A rodenticidal compositions containing 4-hydroxy coumarins

ABSTRACT

The 4-hydroxy coumarins are represented by the formula   IN WHICH R is a member of the group formed by hydrogen, the phenyl, halophenyl, dihalophenyl, nitrophenyl, methoxyphenyl, tolyl, methylene dioxyphenyl and furyl radicals; R1 is a member of the group formed by the methyl, phenyl, halophenyl, nitrophenyl, diphenyl, halodiphenyl, nitrodiphenyl and naphthyl radicals; and R2 is hydrogen or a halogen. These new 4-hydroxy coumarins have very powerful oral anticoagulating actions of the antivitamin K type and are useful as rodenticides.

I United StatesPatent Boschetti et a1.

[ RODENTICIDAL COMPOSITIONS CONTAINING 4-HYDROXY COUMARINS [75] Inventors: Eugene Boschetti, Venissieux;

Darius Molho, Boulogne-sur-Seine; Louis Fontaine, Lyon, all of France [73] Assignee: Lipha, Lyonnaise Industrielle Pharmaceutique, Lyon, France [22] Filed: Mar. 10, 1971 [21] Appl. No.: 123,094

Related US. Application Data [62] Division of Ser. No. 878,876, Nov. 21 1969, Pat. No.

[52] US. Cl..... 424/281, 260/340.5 X, 260/3432 X [51] Int. Cl A0ln 9/28 [58] Field of Search 424/281; 260/3432, 260/3405 x [56] References Cited UNITED STATES PATENTS 2,427,578 9/1947 Stahmann et a]. 260/3432 3,032,557 5/1962 Molho 260/3432 3,135,797 6/1964 Biel 260/3405 X 3,651,091 3/1972 Boschetti et a1. 424/282 Primary Examiner-Albert T. Meyers Assistant ExaminerD. Robinson Attorney-Browdy & Neimark [57] ABSTRACT The 4-hydroxy coumarins are represented by the formula phenyl, halophenyl, nitrophenyl, diphenyl, halodiphenyl, nitrodiphenyl and naphthyl radicals; and

R is hydrogen or a halogen.

These new 4-hydroxy coumarins have very powerful oral anticoagulating actions of the antivitamin K type and are useful as rodenticides.

10 Claims, No Drawings A RODENTICIDAL COMPOSITIONS CONTAINING 4-HYDROXY COUMARINS This application is a divisional of application Ser. No. 878,876 filed Nov. 21, 1969, which is now US. Pat. No. 3,651,091.

Our copending application Ser. No. 689,347, filed Dec. 11, 1967 now U.S. Pat. No. 3,574,234, relates to 4-hydroxy coumarin derivatives, which are represented by the general formula in which X is a member of the group formed by the carbonyl and carbinol radicals;

R is a member of the group formed by hydrogen, the halogens, the methyl and nitro radicals;

and R, is a member of the group formed by the methyl radicals except when X is CO and R is hydrogen and phenyl which is optionally substituted by the halogens, the hydroxy, methyl, methoxy and-nitro radicals.

The present improvement is concerned with new (4'- hydroxy-3'-coumarinyl) compounds, which are substituted by an aliphatic side chain, in which X, in the 1- position, is a substituted carbinol radical as in the copending application, and optionally substituted in the 3-position by an aromatic or heterocyclic radical.

The new 4-hydroxy coumarins of the present improvement are represented-by the formula These new 4-hydroxy coumarins have very powerful oral anticoagulating actions of the antivitamin K type. The hypoprothrombinemiant properties of the compounds of the invention make them of particular inter- 65!.

Furthermore, the 4-hydroxy coumarins of the present improvement are raticides of considerable interest, which cause in rodents, which have consumed food to propiophenone,

which these new compounds are added, a high mortality due to internal hemmorhage.

The 4-hydroxy coumarins of formula (ll) can be obtained by reduction of compounds of formula in which the substituents R, R, and R have the same meanings as in formula (II).

The reduction of the intermediate ketone compounds is effected either by means of aluminium isopropylate or isopropanolic solution, or by a hydride of alkali metal and boron.

It has recently been found, as previously mentioned in the parent patent, that the reduction of the carbonyl group of the intermediate molecules into carbinol grouping increases, depending on the value ofR and R, in the general formula (II), and to a very considerable degree, the hypoprothrombinemiant activity of these compounds.

Certain intermediate ketone compounds which come within the scope of the general formula (Ill), in which R, R, and R have the same meanings as previously, are novel and because of this fact form part of the invention; these are more particularly the following 4- hydroxy coumarins:

(parabromophenyl-2-parabenzoyl)-3-ethyl-4- hydroxy coumarin,

(parachlorophenyl-2-parabenzoyl)-3-ethyl-4- hydroxy coumarin,

(paranitrophenyl-2-'-parabenzoyl)-3-ethyl-4- hydroxy coumarin,

(2'-parabromobenzoyl )-3-ethyl-6-bromo-4-hydroxy coumarin,

(2-parachlor0benzoyl)-3-ethyl-6-chlor0-4-hydroxy coumarin,

(2'-benzoyl)-3-ethyl-6-bromo-4-hydroxy coumarin,

3-(4'-hydroxy-3'-coumarinyl)-3-phenyl parachloropropiophenone,

3-(4'-hydroxy-3'-coumarinyl)-3-paranitrophenyl- 3-(4-hydroxy-3'-coumarinyl)-3-parabromophe'nylpropiophenone,

3-(4-hydroxy-3'-coumarinyl)-3B-phenyl-l-naphthyl-propan- 1 -one,

3-(4-hydroxy-3-coumarinyl)-3-phenyl-(1-(4- diphenylyl)-propan-l-one,

3-(4-hydroxy-3 '-coumarinyl)-3-phenyll 4-chloro- 4'-diphenylyl )-propan- 1 -one,

3-(4-hydroxy-3-coumarinyl)-3-phenyl-1-(4-bromo- 4'-diphenylyl )-propan- 1 -one.

The new compounds according to the application are easily obtained according to one or other of the following two methods.

When R represents hydrogen in the new ketones of formula III, these are easily obtained by condensation of 4-hydroxy coumarin with a mineral acid salt of substituted 3-piperidino propan-l-one, preferably the piperidino propanone hydrochloride of formula HNQCHz-Clir CHr-CHz-CHQ (J)H I o 7.35 g (0.025 mol) of 3-ethyl-( 2-benzoyl)-4-hydroxy coumarin, Mp 152C, prepared by the method described in French Pat. No. 1,206,393 of the 18th Aug. 1958, are placed in suspension in 150 ml of anhydrous methanol. 2.85 g (0.075 mol) of sodium hydrobromide are added in small fractions, while keeping the temperature below 20C. On completing the addition, the mixture is left while stirring for 3 hours at ambient temperature, whereafter it is acidified with 3 ml of acetic acid. The solution is evaporated to dryness and the residue is taken up in 200 ml ofa hot 5% solution of HNaCO This solution is acidified and the compound which is obtained is recrystallised twice from 50% aqueous ethanol. There are obtained 4.3 g (58.5 of a white product melting at 114C (sealed tube Gallenkamp apparatus). Gravimetric analysis: C l-l Q, Molecular weight 293.31

C H calculated 2.96 5.44 5.62

found 73.11

EXAMPLE 2: 3-(4 -hydroxy-3 -coumarinyl 1 parachlorophenyl-propan- 1 -ol CH:-CH:-CHC1 0 nt \0/ v Gravimetric analysis: C, H, ClO molecular weight C H calculated 65.36 4.57 found 4.60

EXAMPLE 3: 3-(4 -hydroxy-3 -coumarinyl)' 1 parabromophenyl-propan- 1 -ol 3.7 g (0.01 mol) of 3-ethyl-2-)parabromobenzoyl)-4- hydroxy coumarin (Mp 230C) are reduced in anhydrous methanol with 1.1 g (0.03 mol) of sodium hydrobromide. After the same operations as in Example 1, the product obtained is solubilised in a 5% HNaCO solution; the solution is acidified and the precipitate is recrystallised from 50% aqueous ethanol. There are. obtained 2.8 g of product, melting at 159C (sealed tube). Gravimetric analysis: C, l-l,,,O.,Br, molecular weight 375.12

calculated found EXAMPLE 4: 3-(4'-hydroxy-3 -coumarinyl)- 1 paranitrophenyl-propan-l-ol OII 3.4 g (0.01 mole) of 3-ethy1(2-paranitrobenzoyl)-4- hydroxy coumarin are reduced with 6.12 g (0.03 mol) of aluminium isopropylate in ml of anhydrous isopropanol. After refluxing for 1 hour, the mixture is poured into iced water and acidified with 10 ml of concentrated HCl. 1t is suction-filtered, washed with water and recrystallised from 50% ethanol. After filtration, it is allowed to crystallise. The product is solubilised in a 5% solution of l-lNaCO and then, after acidification, it is once again crystallised from 50% aqueous ethanol. Yield= 2.3 g, i.e. 68%. The product has a melting point of 178C (sealed tube).

Gravimetric analysis: C, H, NO

calculated found EXAMPLE 5: v 3-(4-hydroxy-3 '-coumarinyl)- l paradiphenylyl-propan- 1 -ol 7.4 g (0.02 mole) of 3-ethyl-(paraphenyl-Z-benzoyl)- 4-hydroxy coumarin (Mp 230C), obtained in accordance with the procedures specified in Example 1, are reduced with 2.3 g (0.06 mol) of sodium hydrobromide in ml of ethanol. After recrystallisation from dilute alcohol, there are obtained 6.3 g of white crystals melting at C (sealed tube). Gravimetric analysis: C I-1 0 372.40

molecular weight calculated found EXAMPLE 6:

3-(4-hydroxy-3'-coumarinyl)-1-(4- bromopara-diphenylyl )-propan- 1 -ol This product is prepared from the 3-ethyl- (parabromophenyl-2-benzoyl)-4-hydroxy coumarin, which is a new compound obtained in the following manner: 6.15 g (0.015 mol) of 3-piperidinoparabromophenyl propiophenone hydro-chloride (TOHUKU YAKKA DlAGAKU KIYO, 4, 68-78, 1957) are refluxed for 3 hours with 2.43 g (0.015 mol) of 4-hydroxy coumarin in 50 ml of pyridine. The solution is poured into iced water and acidified with HCl. The product is washed with boiling acetic acid and then with alcohol. lt melts at 221C (sealed tube).

Yield 4.5 g

Gravimetric analysis: C H BrO molecular weight 5 449.30

C H Br calculated 64.16 3.80 17.79 found 63.96 3.88 17.61

This compound is reduced in the following manner: 4.49 g (0.01 mol) are suspended in 75 ml of isopropanol. 6.12 g (0.03 mol) of aluminum isopropylate are introduced and refluxing takes place for 1 hour. The compound is poured into iced water and acidified to pH 1 with HCl. The product which precipitates is suction-filtered and recrystallised twice from 50% aqueous alcohol. Yield 67% of 3-(4-hydroxy-3-coumarinyl)- 1-(4-bromo para-diphenylyl)-propanol, melting at 202C (sealed tube).

Gravimetric analysis: C H BrO molecular weight C% H% Br calculated 63.87 4.24 17.71 found 6383 4.40 17.88

EXAMPLE 7: 3 -(4-hydroxy-3 '-coumarinyl l -(4- chloro-paradiphenylyl)-propanl-ol c H a calculated 71.21 4.23 found 71.04 4.37

This compound, reduced as in Example 5 with aluminium isopropylate, melts at C (sealed tube) and is only slightly soluble in aqueous alkali medium. Gravimetric analysis: C H ClO molecular weight 406.84

C% 70.86 4.71 found 70.72 4.89

EXAMPLE 8: 3-(4'-hydroxy-3-coumarinyl)-1-(4'- nitropara-diphenylyl )-propan- 1 -ol H% calculated This compound is prepared from the 3-ethyl- (paranitrophenyl-2-benzoyl)-4-hydroxy coumarin, which is a new product prepared in the following manner: 4.86 g (0.03 mol) of 4-hydroxy coumarin, 11.24 g

(0.03 mol) of 3-piperidino-paranitrophenyl propiophenone hydrochloride and 60 ml of pyridine are refluxed for three hours. The solution, poured into cold water, is acidified and the product which precipitates is suction-filtered and crystallised in acetic acid. It melts at 237C (sealed tube). Yield 10.20 g, i.e. 82% Gravimetric analysis: C H NO molecular weight 415.38

C% H% calculated 69.40 4.13 found 4.21

This compound is reduced as in the preceding example with aluminium isopropylate and recrystallised from 60% aqueous ethanol. it melts at C (sealed tube). Yield 59%.

Gravimetric analysis: C H NO molecular weight 417.39

0% 11% j calculated 69.07 4.58 found 68.95 4.63

EXAMPLE 9: 3-(6-bromo-4-hydroxy coumarinyl)-1-para-bromophenyl-propan-1-ol This compound was obtained by reducing the 3- ethyl-(parabromo-2-benzoyl)-6-bromo-4-hydroxy coumarin.

This new intermediary was prepared as in the preceding examples by condensing the 6-bromo-4-hydroxy coumarin with 3-piperidino parabromopropiophenone hydrochloride in pyridine. lt is a white compound, of which the alkaline salts are sparingly soluble in water and melt at 236C.

The reduction was carried out under the following conditions: 6.78 g (0.015 mol) of the above compound are reduced with 9.18 g (0.045 mol) of aluminium isopropylate in 150 ml of anhydrous isopropanol. After recrystallisation from 60% aqueous ethanol, there are obtained 5.5 g (81%) of a compound crystallising as white needles, melting at 168C.

Grav'imetric analysis: C H Br O molecular weight (2% H% calculated 47.60 3.1 1 found 47.76 3.17

EXAMPLE 3-(6'-chloro-4'-hydroxy-3 coumarinyl)-1-para-chlorophenyl-propan-l-ol calculated -bromo-59.l9 3.85

found 59.31 4.04

EXAMPLE 1 l: 3-( 6'-bromo-4-hydroxy-3 coumarinyl l -phenyl-propan- 1 -ol on Br CHz-Cl-h-CHQ 7.46 g (0.02 mol) of 3-ethyl-(2'-benzoyl)-6-bromo- 4-hydroxy coumarin (Mp 180C) are reduced with 12.24 g (0.06 mol) of aluminium isopropylate in 150 ml of anhydrous isopropanol. After refluxing for 1 hour, the solution is poured into iced water and acidified with concentrated HCl. The white precipitate is suction-filtered after standing for 12 hours. It is recrystallised from 50% aqueous ethanol. Yield 6.1 g, i.e. 81%. Melting point in a sealed tube: 187C.

Gravimetric analysis: C H BrQ, molecular weight (2% H% calculated 57.59 4.03 found 57.51 4.15

EXAMPLE l2: 4-(4'-hydroxy-3'-coumarinyl)-4-phenyl-butan-Z-ol 4.62 g (0.015 mol) of 4-(4-hydroxy-3'-coumarinyl)- 4-phenyl-butan-2-one (.1. Am. Chem. Soc., 66 902-6, 1944) are refluxed for 1 hour with 9.18 g (0.045 mol) of aluminium isopropylate in 120 m1 of anhydrous isopropanol. The mixture is poured into 600 ml of iced water containing 20 ml of 6N-HC1. The oil which decants is taken up in a 10% HNaCO solution. filtered and the alkaline solution is acidified. The product precipitates in the form of a white powder.

A second treatment is carried out with bicarbonate in the cold. The product is suction-filtered and dried under vacuum at ambient temperature. It shows a pasty fusion at 9496C (sealed tube). Yield 3.25 g. Gravimetric analysis: C d-1, 0 molecular weight 310.33

. C% H% calculated 73.53 5.85 found 73.37 5.80

EXAMPLE 13: 4-(4-hydroxy-3 -coumarinyl )-4- parachlorophenyl-butan-2-ol HCH:CHCH:

As in Example 12, 10.27 g (0.03 mol) of 4-(4'- hydroxy-3-coumarinyl)-4-parachlorophenyl-butan- 2-one (W.G. Stoll, Proc. lnterm. Conf. Thromb. Embol. 1954, 244-50), are reduced with 18.36 g (0.09 mol) of aluminium isopropylate.

The product which is obtained (6.35 g yield 61.5%) shows a pasty fusion at 9597C (sealed tube). Gravimetric analysis: C H ClO molecular weight 344.78

C% H% calculated 66.18 4.97 found 66.03 5 .04

EXAMPLE l4: 4-(4'-hydroxy-3'-coumarinyl)-4- paramethoxy phenyl-butan-2-ol OCH;

6.76 g (0.02 mol) of 4-(4'-hydroxy-3-coumarinyl)-4- paramethoxy phenoxy phenyl-butan-Z-one (J. Am. Chem. Soc., 66; 902-6, 1944) are treated with 12.24 g (0.06 mol) of aluminium isopropylate in cc of isopropanol under the conditions previously described.

There are obtained 6.2 g (91%) of a white compound which is soluble in the cold in a 5% bicarbonate solution which, after recrystallisation from a mixture of acetone and water, melts at 78C (sealed tube). Gravimetric analysis: c ii o. molecular weight 3- 40.36

i c% 1% calculated 70.58 5.92 found 70.78 6.11

EXAMPLE l5: 4-(4-hydroxy-3'-coumarinyl)-4- (3 ',4-dichlorophenyl)-butan-2-ol 5 H-CHr-CH-CH:

7.4 g (0.02 mol) of 4-(4'-hydroxy-3'-coumarinyl)-4- (3',4'-dich1orophenyl)-butan-2-one (Mp 176C) reduced with 0.03 mol of isopropylate, lead with a yield of 93% to a white compound which has good solubility in a 5% HNaCO solution and melting at 92C (sealed tube pasty fusion).

Gravimetric analysis: C l-l Cl O molecular weight 379.23

calculated 60.17 4.25

found 60.08 4.30

EXAMPLE l6: 4-(4'-hydroxy-3 '-coumarinyl)-4- paratolyl-butan-Z-ol (BE-Cl-Ix-ZH-CH: f H

8.05 g (0.025 mol) of 4-(4'-hydroxy-3-coumariny1)- 4-paratoly1-butan-2-one are reduced under the conditions of the preceding examples with 15.3 g (0.075 mol) of aluminium isopropylate in 150 ml of isopropanol. After passing through a bicarbonate solution, acidification and recrystallisation from acetone and water, there are obtained 5.70 g (70%) of a white compound melting at 1 19C (sealed tube).

Gravimetric analysis: C H O molecular weight 7.04 g (0.02 mol) of 4-(4'-hydroxy-3'-coumarinyl)- 4-(3,4'-methylene dioxyphenyl)-butan-2-one are reduced with 12.24 g (0.06 mol) of aluminium isopropylate. The product obtained, with a yield of 87%, shows a pasty fusion at 96C in a sealed tube. Gravimetric analysis: C d-1, 0 molecular weight 354.34

calculated 67.79 5.12

found 67.64 5.23

EXAMPLE 18: 4-(4'-hydroxy-3 -coumarinyl )-4- (paranitrophenyl )-butan-2-ol 7.06 g (0.02 mol) of 4-(4'-hydroxy-3'-coumarinyl)- 4-paranitrophenyl-butan-2-one are reduced with 12.24 g (0.03 mol) of aluminium isopropylate. There are obtained 6.6 g of a white compound melting at 106C (acetone-water) in a sealed tube, corresponding to a yield of 93%.

Gravimetric analysis: C H NO molecular weight C% H% calculated 64.21 4.82 found 64.04 4.96

EXAMPLE l9: 4-(4'-hydroxy-3 -coumarinyl)-4- (metanitroghenyl )-butan-2-ol Starting with 7.06 g (0.02 mole) of 4-(4'-hydroxy-3- coumarinyl)-4-(metanitrophenyl)-butan-2-one, reduced with 12.24 g (0.03 mol) of aluminium isopropylate, there is obtained, with a yield of 91.50%, 6.4 g of 4-(4-hydroxy-3'-coumarinyl)4-(metanitrophenyl)- butanol, melting at 96C (sealed tube).

Gravimetric analysis: C H NO molecular weight 355.33

C% H% calculated 64.21 4.82 found 64.08 4.90

EXAMPLE 20: furyl-butan-Z-ol 4-( 4 -hydroxy-3 -coumariny1)-a-4- Starting with 8.94 g (0.03 mol) of 4-(4-hydroxy-3- coumarinyl)-a-4-furyl-butan-2-one, reduced with 18.36 g (0.09 mol) of aluminium isopropylate in 150 m1 of isopropanol, there is obtained a precipitate which, after being solubilised in HNaCO acidified and recrystallised from hexane in the presence of a small quantity of acetone, melts at 77C in a sealed tube. Yield 6 g, i.e. 66%.

Gravimetric analysis: C I-1, molecular weight 300.30

C% 8% calculated 67.99 5.37 found 68.12 5.52

EXAMPLE 21: 3-(4'-hydroxy-3'-coumarinyl)-1,3- diphenyl-propan- 1 -ol OH i 18.5 g (0.05 mol) of 3-(4'-hydroxy-3'-coumarinyl)- 3 phenyl propiophenone and 30.6 g (0.15 mol) of aluminium isopropylate are heated under reflux for 1 hour. The solution is poured into acidulated iced water and the product which precipitates is taken up in a hot 10% sodium bicarbonate solution. The alkaline solu tion is acidified. The product which precipitates, dried under vacuum, melts at 85C (sealed tube).

As set out in the parent patent, these molecules have two asymmetrical carbon atoms and it can be assumed that the compounds obtained are a mixture of diastereo isomers. With certain compounds, when the end of the chain is aromatic, it has been possible by crystallisation to obtain one of the diastereo isomers having a melting point decidedly higher than the mixture. Analysis of the mixture, which melts at 85C and is obtained with a yield of 70%, is as follows:

Gravimetric analysis: C H Q, molecular weight 372.40

C% (4% calculated 77.40 5.41 77.53 5.46

found 0% me calculated 77.40 5.41 found 77.20 5.42

EXAMPLE 22: 3-(4-hydroxy-3 '-coum arinyl)-3- parachlorophenyl- 1 -phenyl-propan- 1 -ol oH-ca,cn O 1.. 0 7 f 16.2 g (0.04 mol) of 3-(4'-hydroxy-3'-coumariny1)- 3-parachloropheny1-propiophenone are reduced with 24.5 g (0.12 mol) of aluminium isopropylate in 300 ml of anhydrous isopropanol. After refluxing for 1 hour,

' the solution is poured into acidulated water and the product which precipitates is taken up in 600 ml of hot 5% l-lNaCO The solution is filtered and acidified. There are obtained 12.2 g ofa white compound 7 which melts at C (pasty fusion) (sealed tube).

Gravimetric analysis: C l- 00 molecular weight 406.84

C H% calculated 70.85 4.7 I found 70.66 4.83

After being recrystallised twice from a mixture of methyl isobutyl ketone and hexane, the diastereo isomer is obtained, which melts at 168C (sealed tube). Gravimetric analysis: C H ClQ, molecular weight 406.84

C% H% calculated 70.85 4.71 found 70.83 4.69

EXAMPLE 23: 3-(4'-hydroxy-3-coumarinyl)-1,3-di- (parachlorophenyl )-propan- 1 -ol C% 11% Cl% calculated 65.32 4.1l 16.07 found 65.12 4.30 15.87

EXAMPLE 24: 3-(4'-hydroxy-3 -coumarinyl )-3- phenyl- 1 -para-chlorophenyl-propan- 1-01 This compound is obtained from the 3-(4-hydroxy- 3 '-coumarinyl )-3-phenyl-parachloropropiophenone which is a new compound obtained in the following manner: 17.8 g (0.11 mol) of 4-hydroxy coumarin are condensed with 24.3 g (0.1 mol) of benzylidene parachloroacetophenone in the presence of 80 mg of hexamethyelene imine in 160 ml of water. The mixture is left under reflux for 5 hours, the organic phase is decanted and crystallised in benzene. The product, C H ClO melts at 165C (sealed tube).

The ketone compound is reduced under the usual conditions: 16.2 g (0.04 mol) and 24.5 g (0.12 mol) of aluminium isopropylate in 300 ml of isopropanol. After acidification of a solution in sodium bicarbonate, there are obtained 12.7 g (77%) of a white compound melting at 95C (sealed tube) Gravimetric analysis: C I-1 C molecular weight 406.84

C% 11% Cl% calculated 70.85 4.71 8.71 found 71.02 4.91 8.52

By crystallisation in a mixture of methyl isobutyl ketone and hexane, the diastereo isomer melting at 175C (sealed tube) is obtained: Gravimetric analysis: C l-l C10 molecular weight 406.84

calculated 70.85 4.71 8.71 found 70.87 4.92 8.78

EXAMPLE 25: 3-(4'-hydroxy-4'-cournarinyl)-3- paranitrophenyl- 1 -phenyl-propan- 1 -ol The compound of this example was prepared from the 3-(4'-hydroxy-3'-coumarinyl)-3-paranitrophenyl propiophenone, itself obtained in the following manner:

paranitrobenzylidene acetophenone 4 hydroxy coumarin piperidine dioxane 25.3 g (0.1 mol) 17.8 g (0.11 mol) 0.89 g 100 cc c% 11% N% calculated 69.06 4.59 3.35 found 68.97 4.70 3.38

Two recrystallisations in the mixture of methyl isobutyl ketone and hexane supply an isomer melting at 161162C (sealed tube).

Gravimetric analysis: C H NO parabromophenyl- 1 -phenyl-propan l-ol The compound of this example is prepared from 3- (4-hydroxy-3-coumarinyl)-3-parabromophenyl propiophenone.

This intermediary is obtained in the following manner: the following are heated for 7 hours under reflux:

14.3 g (0.88 mol) of 4-hydroxy coumarin 23.0 g (0.08 mol) of parabromobenzylidene acetophenone 0.7 g of piperidine 80 m1 of dioxane.

The mass is caused to crystallise after evaporation of the dioxane by means of acetone. The substance is suction-filtered and recrystallised from ethanol. There are obtained 22.3 g (62%) of white crystals, melting at 162C (C H, BrO.,).

This intermediary is reduced with a yield of 73% as in the preceding example. The 3-(4'-hydroxy-3'- coumarinyl)-3-parabromophenyl-1-phenyl-propan- 1 01 has a pasty fusion at 100C (sealed tube). Gravimetric analysis: C l-1 BrO molecular weight 451.31

11% 31% calculated 63.87 4.24 17.71 found 63.76 4.36 17.59

c% 14% Br% 'calculated 63.87 4.24 17.71 found 63.82 4.42 17.77

EXAMPLE 27: 3-(4'-hydroxy-3 -coumarinyl)-3- phenyll -,B-naphthyl-propanl-ol The compound of this example was obtained from the 3-(4'-hydroxy-3-coumarinyl)-3,8-phenyl-l-naphthyl-propan-l-one. This intermediary is obtained by heating the following mixture for 7 hours under reflux:

benzylidene-B-acetonaphthone 25.8 g (0.1 mol) 4-hydroxy coumarin 17.8 g (0.1 1 mol) piperidine 0.9 g

dioxane 100 cc There are obtained 26.3 g of white crystals (ethanol) melting at 138C (sealed tube).

Gravimetric analysis: C l-1 molecular weight 420.44

C"7c 11% calculated 79.99 4.79 found 79.82 4.95

C% 11% calculated 79.60 5.25 found 79.50 5.09

EXAMPLE 28: 3-(4'-hydroxy-3-coumarinyl3-phenyll-(4-diphenyl)-propan- 1 -ol CeHs The compound of this example is obtained from 3- (4'-hydroxy-3 '-coumarinyl )-3-phenyl-1-(4'-diphenyl)- propan-l-one.

This intermediary is obtained by the following being heated for 8 hours under reflux:

benzylidene paraphenyl acetophenone 23.7 g (0.08 mol) 4-hydroxy coumarin 14.3 g (0.088 mol) piperidine 0.7 g

dioxane 80 ml There are obtained 18.2 g (52%), melting at 172C (sealed tube), after two recrystallisations from ethyl acetate.

Percentage analysis: C H O molecular weight 446.- 48

C% H% calculated 80.70 4.97 found 80.65 4.91

This intermediary was reduced with a yield of 80%, using a mixture of isopropanol and dioxane (75-25).

After two passages in the sodium salt stage (hot bicarbonate), a white product is obtained which melts at 1 10C (sealed tube).

G l-1 0., molecular weight 448.49

C% 11% calculated 80.34 5.39 found 80.35 5.39

An isomer melting at 194C is isolated in the mixture of methyl isobutyl ketone and hexane.

Gravimetric analysis: 0 11 0 molecular weight 448.49

phenyll 4-chloro-4'-diphenylyl )propan- 1 -ol.

aHs

OH O was obtained from the 3-(4-hydroxy-3-coumariny1)- 3-phenyll 4-ch10r0-4-diphenylyl )propan- 1 -one, which compound is itself prepared in the following manner:

22.3 g (0.07 mol) of benzylidene para-(4'- chlorophenyl)-acetophenone 12.5 g (0.77 mol) of 4-hydroxy coumarin 0.70 g piperidine 70 ml dioxane are refluxed for 7 hours.

There are obtained 22.5 g (67%) of a compound melting at 182C (sealed tube), after crystallisation'in a mixture of alcohol and dioxane (C l-1 C10 16.8 g (0.035 mol) of this compound are reduced with 21.4 g of aluminium isopropylate in 260 ml of isopropanol and 50 ml of dioxane. After refluxing for 1 hour, the solu- 1 tion poured into 1000 m1 of cold water containing 100 m1 of 21 Be HCl allows the precipitation of a coloured product, which is purified by passage in solution into hot 5% llNaCO After acidification, the white product precipitates. After drying under vacuum, there are ob- -tained 13.2 g (78%) of a compound melting at l05108C (sealed tube). Gravimetric analysis: C H CIO molecular weight 482.93

calculated 74.60 4.80 1.35 found 74.43 4.82 7.22

EXAMPLE 30: 3-(4-hydroxy-3 '-coumariny1)-3- phenyl-1-(4-bromo-4-diphenylyl)propan-l-ol 1 0 s fiHAJHPCi-FQGM 0H \o/ O a. 3-(4'-hydroxy-3'-coumariny1)-3-phenyll 4-bromo- 4 -diphenylyl)propan-1-one.

The following are heated for 7 hours under reflux:

18.2 g (0.05 mol) of benzylidene para-(4'- bromophenyl)acetophenone 8.9 g (0.055 mol) of 4-hydroxy coumarin 0.45 g of piperidine 50 ml of dioxane.

The solvent is evaporated under vacuum and the residue is recrystallized from a mixture of alcohol and dioxane. There are obtained 16.2 g (62%) of a white compound melting at C (sealed tube). C H- BrO b. 13.1 g (0.025 mol) of this compound are reduced with 15.3 g (0.075 mol) of aluminium isopropylate in PHARMACOLOGICAL RESULTS The rat-destroying activity was investigated in connection with the adult white rat. The tests were carried out on batches of ten animals. They receive for one day wheat containing the compound to be investigated, after having received for several days a feed consisting of ordinary wheat. The poisoned food was replaced from the second day by ordinary wheat.

When, in the general formula:

calculated found R H R c l-l R C li. C l-l Br (L.M. 637) the results are as follows:

Compounds Concentration Mortality 3-ethyl-( l'- phenyl-2'-acetyl)-4 0.00257: 1/10 hydroxycoumarin L.M. 636 0.0025% 9/l0 L.M10330 The poisoned baits were prepared in the following manner:

In a first period, the wheat was impregnated with an alcoholic solution of the toxic substance:

wheat 1 Kg toxic compound 25 mg ethanol 50 cc.

The solvent is evaporated and the wheat is colored with a dye solution:

organol red dye 100 mg valine oil 20 cc While the most active compounds also have a good action in killing mice, it was seen that the compound for which, in the general formula: R H R H and R C l-l C l-l Br (L.M. 568) has a much higher effect in killing mice than in killing rats.

The mouse-killing test of this product was carried out LII on male N.M.R.l mice weighing 25 g. The bait with 0.005% of mol. weight 568 was given for two days after one week of normal wheat, the food starting from the third day being once again normal wheat.

The mortality observed was 22/30 mice between the fourth and eighth days.

In the same concentration, the L.M. 568 (product given for one day under the conditions previously described for the rat-killing test) only produced two deaths out of ten.

What is claimed is:

l. A rodenticidal composition comprising a rodenticidally effective amount of an active compound of the formula:

wherein R is hydrogen, phenyl, halophenyl, dihalophenyl, nitrophenyl, methoxyphenyl, tolyl, methylene dioxphenyl or furyl,

R is methyl, phenyl, halophenyl, nitrophenyl, diphenyl, halodiphenyl, nitrodiphenyl or naphthyl, and

R is hydrogen or a halogen; and a rodent feed as bait.

2. The rodenticidal composition of claim 1 wherein said feed is wheat.

3. The rodenticidal composition of claim 1 wherein said active ingredient is selected from the group consisting of 3-(4-hydroxy-3-coumarinyl)-3-phenyl-l-(4- chloro-4'-diphenylyl) propan-l-ol and 3 4'-hydroxy-3'-coumarinyl )-3-phenyll 4-bromo- 4'-diphenylyl) propan-l-ol.

4. The rodenticidal composition of claim 1 wherein said active ingredient is 3-(4'-hydroxy-3-coumarinyl) -l-(4-bromopara-diphenylyl)-propan-1-ol.

5. The rodenticidal composition of claim 1 wherein R is hydrogen.

6. The rodenticidal composition of claim 1 wherein R is hydrogen, R is halodiphenyl and R is hydrogen or phenyl.

7. The rodenticidal composition of claim 6 wherein said active compound is present in a concentration between 0.0025 percent and 0.005 percent.

8, The rodenticidal composition of claim 3 wherein said active compound is present in a concentration of about 0.0025 percent.

9. The rodenticidal composition of claim 4 whereinsaid active compound is present in a concentration of about 0.005 percent.

10. The method of killing rodents comprising applying to the rodent inhabiting locus a rodenticidally effective amount of the composition of claim 1.

UNITED STATES PATENT OFFICE I CERTIFICATE OF CORRECTION Patent No. 3,764,693 Dated OctoberZ, 1973 Inventor) Boscahetti et a1,

It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:

Column 7, line 36, delete "-bromo-";

same line, delete "3.85" and insert therefor 3.86--.

Column 17,

"Mortality" delete "L.M. etc" and insert therefor 9/10-- between lines 38 'and"39,insert L.M. 637 0.002575 lO/l0--.

si ned arid sealed this 1mm day of May 197E.

(SEAL) Atte st:

EDWARD M.FLETGHER,JR. I C. MARSHALL DANN Commissioner of Patents Attesting Officer FORM PO-IOSO (10-69) COMM Dc 503" p i v.5. GOVEIINMINT FIINTING OFFICE "I. 0l-8l 

2. The rodenticidal composition of claim 1 wherein said feed is wheat.
 3. The rodenticidal composition of claim 1 wherein said active ingredient is selected from the group consisting of 3-(4''-hydroxy-3''-coumarinyl)-3-phenyl-1-(4-chloro-4''-diphenylyl) propan-1-ol and 3-(4''-hydroxy-3''-coumarinyl)-3-phenyl-1-(4-bromo-4''-diphenylyl) propan-1-ol.
 4. The rodenticidal composition of claim 1 wherein said active ingredient is 3-(4''-hydroxy-3''-coumarinyl) -1-(4''-bromopara-diphenylyl)-propan-1-ol.
 5. The rodenticidal composition of claim 1 wherein R2 is hydrogen.
 6. The rodenticidal composition of claim 1 wherein R2 is hydrogen, R1 is halodiphenyl and R is hydrogen or phenyl.
 7. The rodenticidal composition of claim 6 wherein said active compound is present in a concentration between 0.0025 percent and 0.005 percent.
 8. The rodenticidal composition of claim 3 wherein said active compound is present in a concentration of about 0.0025 percent.
 9. The rodenticidal composition of claim 4 wherein said active compound is present in a concentration of about 0.005 percent.
 10. The method of killing rodents comprising applying to the rodent inhabiting locus a rodenticidally effective amount of the composition of claim
 1. 